Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the Multiethnic Cohort Adiposity Phenotype Study

被引:145
作者
Fu, Benjamin C. [1 ,2 ,3 ]
Hullar, Meredith A. J. [1 ]
Randolph, Timothy W. [1 ]
Franke, Adrian A. [4 ]
Monroe, Kristine R. [5 ]
Cheng, Iona [6 ]
Wilkens, Lynne R. [4 ]
Shepherd, John A. [4 ]
Madeleine, Margaret M. [1 ]
Le Marchand, Loic [4 ]
Lim, Unhee [4 ]
Lampe, Johanna W. [1 ,2 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA
[2] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
[3] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
[4] Univ Hawaii Manoa, Univ Hawaii Canc Ctr, Epidemiol Program, Honolulu, HI 96822 USA
[5] Univ Southern Calif, Dept Prevent Med, Los Angeles, CA 90007 USA
[6] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA
关键词
TMAO; choline; carnitine; betaine; inflammation; cardiometabolic; biomarkers; microbiome; HOMEOSTASIS MODEL ASSESSMENT; CARDIOVASCULAR-DISEASE; GUT MICROBIOTA; FATTY-ACIDS; METABOLISM; PHOSPHATIDYLCHOLINE; SERUM; NUTRIENT; ARCHAEA; GLUCOSE;
D O I
10.1093/ajcn/nqaa015
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Background: Trimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well understood and few human studies have investigated microbes involved in its production. Objectives: Our study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO. Methods: We conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60-77 y) in the Multiethnic Cohort Study. Plasma concentrations of TMAO and its precursors were measured by LC-tandem MS. We also analyzed fasting blood for markers of inflammation, glucose and insulin, cholesterol, and triglycerides (TGs), and further measured blood pressure. Fecal microbiome composition was evaluated by sequencing the 16S ribosomal RNA gene V1V3 region. Associations of TMAO and its precursors with disease risk biomarkers were assessed by multivariable linear regression, whereas associations between TMAO and the fecal microbiome were assessed by permutational multivariate ANOVA and hurdle regression models using the negative binomial distribution. Results: Median (IQR) concentration of plasma TMAO was 3.05 mu mol/L (2.10-4.60 mu mol/L). Higher concentrations of TMAO and carnitine, and lower concentrations of betaine, were associated with greater insulin resistance (all P < 0.02). Choline was associated with higher systolic blood pressure, TGs, lipopolysaccharide-binding protein, and lower HDL cholesterol (P ranging from <0.001 to 0.03), reflecting an adverse cardiometabolic risk profile. TMAO was associated with abundance of 13 genera (false discovery rate< 0.05), including Prevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to the families Ruminococcaceae and Lachnospiraceae, as well as the methanogen Methanobrevibacter Conclusions: Plasma TMAO concentrations were associated with a number of trimethylamine-producing bacterial taxa, and, along with its precursors, may contribute to inflammatory and cardiometabolic risk pathways.
引用
收藏
页码:1226 / 1234
页数:9
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